IL210836A - Organic compounds, process for preparation, pharmacological preparations including them and their use in the manufacture of drugs to treat inflammatory or allergy conditions - Google Patents
Organic compounds, process for preparation, pharmacological preparations including them and their use in the manufacture of drugs to treat inflammatory or allergy conditionsInfo
- Publication number
- IL210836A IL210836A IL210836A IL21083611A IL210836A IL 210836 A IL210836 A IL 210836A IL 210836 A IL210836 A IL 210836A IL 21083611 A IL21083611 A IL 21083611A IL 210836 A IL210836 A IL 210836A
- Authority
- IL
- Israel
- Prior art keywords
- optionally substituted
- groups
- alkyl
- hydroxy
- group optionally
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 30
- 230000002757 inflammatory effect Effects 0.000 title description 15
- 238000002360 preparation method Methods 0.000 title description 10
- 239000003814 drug Substances 0.000 title description 9
- 239000008194 pharmaceutical composition Substances 0.000 title description 8
- 206010027654 Allergic conditions Diseases 0.000 title description 6
- 150000002894 organic compounds Chemical class 0.000 title description 4
- 230000008569 process Effects 0.000 title description 4
- 238000004519 manufacturing process Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 140
- 229910052739 hydrogen Inorganic materials 0.000 claims description 65
- 125000000623 heterocyclic group Chemical group 0.000 claims description 44
- 125000005843 halogen group Chemical group 0.000 claims description 36
- 125000002837 carbocyclic group Chemical group 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 125000004122 cyclic group Chemical group 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 125000001033 ether group Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000002947 alkylene group Chemical group 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 108091008648 NR7C Proteins 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 150000004677 hydrates Chemical class 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 4
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 4
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 3
- 101100212791 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YBL068W-A gene Proteins 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 101000585507 Solanum tuberosum Cytochrome b-c1 complex subunit 7 Proteins 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- YAKBFNXIVPNQSN-NDPMZMCLSA-N 3-[4-chloro-2-hydroxy-3-[[(4s)-4-hydroxy-1,2-oxazolidin-2-yl]sulfonyl]anilino]-4-[[(1r)-1-[(2r,5r)-5-methyloxolan-2-yl]propyl]amino]cyclobut-3-ene-1,2-dione Chemical compound N([C@H](CC)[C@@H]1O[C@H](C)CC1)C(C(C1=O)=O)=C1NC(C=1O)=CC=C(Cl)C=1S(=O)(=O)N1C[C@H](O)CO1 YAKBFNXIVPNQSN-NDPMZMCLSA-N 0.000 claims 1
- QZQXWAQETULWCA-OCCSQVGLSA-N 3-[[3,4-dioxo-2-[[(1r)-1-[(2s)-oxolan-2-yl]propyl]amino]cyclobuten-1-yl]amino]-n-ethyl-2-hydroxy-n-methoxybenzenesulfonamide Chemical compound N([C@H](CC)[C@H]1OCCC1)C(C(C1=O)=O)=C1NC1=CC=CC(S(=O)(=O)N(CC)OC)=C1O QZQXWAQETULWCA-OCCSQVGLSA-N 0.000 claims 1
- JKZBOPKZKLCRDR-GFCCVEGCSA-N 6-chloro-2-hydroxy-n-methoxy-n-methyl-3-[[2-[[(1r)-1-(5-methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]benzenesulfonamide Chemical compound N([C@H](CC)C=1OC(C)=CC=1)C(C(C1=O)=O)=C1NC1=CC=C(Cl)C(S(=O)(=O)N(C)OC)=C1O JKZBOPKZKLCRDR-GFCCVEGCSA-N 0.000 claims 1
- GOVVZKTWJFVEFJ-MPKXVKKWSA-N 6-chloro-2-hydroxy-n-methoxy-n-methyl-3-[[2-[[(1r)-1-[(2r,5r)-5-methyloxolan-2-yl]propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]benzenesulfonamide Chemical compound N([C@H](CC)[C@@H]1O[C@H](C)CC1)C(C(C1=O)=O)=C1NC1=CC=C(Cl)C(S(=O)(=O)N(C)OC)=C1O GOVVZKTWJFVEFJ-MPKXVKKWSA-N 0.000 claims 1
- RIWDUWXJMRLUEE-UHFFFAOYSA-N 6-chloro-3-[[2-(cyclopentylamino)-3,4-dioxocyclobuten-1-yl]amino]-2-hydroxy-n-methoxy-n-methylbenzenesulfonamide Chemical compound CON(C)S(=O)(=O)C1=C(Cl)C=CC(NC=2C(C(=O)C=2NC2CCCC2)=O)=C1O RIWDUWXJMRLUEE-UHFFFAOYSA-N 0.000 claims 1
- JKBDSUOSMHIBOB-UHFFFAOYSA-N 6-chloro-3-[[2-(heptan-4-ylamino)-3,4-dioxocyclobuten-1-yl]amino]-2-hydroxy-n-methoxy-n-methylbenzenesulfonamide Chemical compound O=C1C(=O)C(NC(CCC)CCC)=C1NC1=CC=C(Cl)C(S(=O)(=O)N(C)OC)=C1O JKBDSUOSMHIBOB-UHFFFAOYSA-N 0.000 claims 1
- HZMAFSFOEIRHAL-UHFFFAOYSA-N 6-chloro-3-[[3,4-dioxo-2-(pentan-3-ylamino)cyclobuten-1-yl]amino]-2-hydroxy-n-methoxy-n-methylbenzenesulfonamide Chemical compound O=C1C(=O)C(NC(CC)CC)=C1NC1=CC=C(Cl)C(S(=O)(=O)N(C)OC)=C1O HZMAFSFOEIRHAL-UHFFFAOYSA-N 0.000 claims 1
- INLUZLJTWAQRGI-UHFFFAOYSA-N 6-chloro-3-[[3,4-dioxo-2-(propan-2-ylamino)cyclobuten-1-yl]amino]-2-hydroxy-n-methoxy-n-methylbenzenesulfonamide Chemical compound CON(C)S(=O)(=O)C1=C(Cl)C=CC(NC=2C(C(=O)C=2NC(C)C)=O)=C1O INLUZLJTWAQRGI-UHFFFAOYSA-N 0.000 claims 1
- DWTBXJQVFDZAFB-UHFFFAOYSA-N 6-chloro-3-[[3,4-dioxo-2-(propan-2-ylamino)cyclobuten-1-yl]amino]-n-ethyl-2-hydroxy-n-methoxybenzenesulfonamide Chemical compound CCN(OC)S(=O)(=O)C1=C(Cl)C=CC(NC=2C(C(=O)C=2NC(C)C)=O)=C1O DWTBXJQVFDZAFB-UHFFFAOYSA-N 0.000 claims 1
- ZCIFQOODWJAYAH-JTDNENJMSA-N 6-chloro-3-[[3,4-dioxo-2-[[(1r)-1-(oxolan-2-yl)propyl]amino]cyclobuten-1-yl]amino]-2-hydroxy-n-methoxy-n-methylbenzenesulfonamide Chemical compound N([C@H](CC)C1OCCC1)C(C(C1=O)=O)=C1NC1=CC=C(Cl)C(S(=O)(=O)N(C)OC)=C1O ZCIFQOODWJAYAH-JTDNENJMSA-N 0.000 claims 1
- NVKNERVQAPUTRC-PUODRLBUSA-N 6-chloro-3-[[3,4-dioxo-2-[[(1r)-1-(oxolan-2-yl)propyl]amino]cyclobuten-1-yl]amino]-n-ethyl-2-hydroxy-n-methoxybenzenesulfonamide Chemical compound N([C@H](CC)C1OCCC1)C(C(C1=O)=O)=C1NC1=CC=C(Cl)C(S(=O)(=O)N(CC)OC)=C1O NVKNERVQAPUTRC-PUODRLBUSA-N 0.000 claims 1
- OMSPSJDPPPHAII-GFCCVEGCSA-N 6-chloro-3-[[3,4-dioxo-2-[[(1r)-1-pyridin-2-ylpropyl]amino]cyclobuten-1-yl]amino]-2-hydroxy-n-methoxy-n-methylbenzenesulfonamide Chemical compound N([C@H](CC)C=1N=CC=CC=1)C(C(C1=O)=O)=C1NC1=CC=C(Cl)C(S(=O)(=O)N(C)OC)=C1O OMSPSJDPPPHAII-GFCCVEGCSA-N 0.000 claims 1
- QFQBTUCEDNSPRH-CYBMUJFWSA-N 6-chloro-n-ethyl-2-hydroxy-n-methoxy-3-[[2-[[(1r)-1-(5-methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]benzenesulfonamide Chemical compound N([C@H](CC)C=1OC(C)=CC=1)C(C(C1=O)=O)=C1NC1=CC=C(Cl)C(S(=O)(=O)N(CC)OC)=C1O QFQBTUCEDNSPRH-CYBMUJFWSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 80
- 239000000543 intermediate Substances 0.000 description 50
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 40
- 239000000203 mixture Substances 0.000 description 40
- 239000000243 solution Substances 0.000 description 40
- 239000011541 reaction mixture Substances 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 28
- 239000007787 solid Substances 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- -1 3,4-di-substituted cyclobutene-1 ,2-diones Chemical class 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 102000002791 Interleukin-8B Receptors Human genes 0.000 description 11
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 11
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 239000005557 antagonist Substances 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 7
- 108090001007 Interleukin-8 Proteins 0.000 description 7
- 102000004890 Interleukin-8 Human genes 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 210000000440 neutrophil Anatomy 0.000 description 7
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 6
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- 208000027771 Obstructive airways disease Diseases 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000003643 water by type Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 102100034221 Growth-regulated alpha protein Human genes 0.000 description 5
- 101001069921 Homo sapiens Growth-regulated alpha protein Proteins 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 206010006451 bronchitis Diseases 0.000 description 5
- 230000003182 bronchodilatating effect Effects 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 102100036150 C-X-C motif chemokine 5 Human genes 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- 101000947186 Homo sapiens C-X-C motif chemokine 5 Proteins 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
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- 229940124623 antihistamine drug Drugs 0.000 description 4
- 239000000739 antihistaminic agent Substances 0.000 description 4
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- 150000001721 carbon Chemical group 0.000 description 4
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- 230000035605 chemotaxis Effects 0.000 description 4
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- 229940079593 drug Drugs 0.000 description 4
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- 239000012528 membrane Substances 0.000 description 4
- 201000006417 multiple sclerosis Diseases 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- AQFLVLHRZFLDDV-SECBINFHSA-N (1r)-1-phenylpropan-1-amine Chemical compound CC[C@@H](N)C1=CC=CC=C1 AQFLVLHRZFLDDV-SECBINFHSA-N 0.000 description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- FDHABSIKPAIOPZ-UHFFFAOYSA-N 6-chloro-3-[(2-ethoxy-3,4-dioxocyclobuten-1-yl)amino]-2-hydroxy-n-methoxy-n-methylbenzenesulfonamide Chemical compound O=C1C(=O)C(OCC)=C1NC1=CC=C(Cl)C(S(=O)(=O)N(C)OC)=C1O FDHABSIKPAIOPZ-UHFFFAOYSA-N 0.000 description 3
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- 206010028980 Neoplasm Diseases 0.000 description 3
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
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- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 3
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- PQPFFKCJENSZKL-UHFFFAOYSA-N pentan-3-amine Chemical compound CCC(N)CC PQPFFKCJENSZKL-UHFFFAOYSA-N 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 3
- BHONVBPCNYEAAB-ULUSZKPHSA-N (1r)-1-(oxolan-2-yl)propan-1-amine Chemical compound CC[C@@H](N)C1CCCO1 BHONVBPCNYEAAB-ULUSZKPHSA-N 0.000 description 2
- BHRZNVHARXXAHW-SCSAIBSYSA-N (2r)-butan-2-amine Chemical compound CC[C@@H](C)N BHRZNVHARXXAHW-SCSAIBSYSA-N 0.000 description 2
- GNVRFBMUQOGBRH-ZCFIWIBFSA-N (2r)-n-methoxy-n-methyloxolane-2-carboxamide Chemical compound CON(C)C(=O)[C@H]1CCCO1 GNVRFBMUQOGBRH-ZCFIWIBFSA-N 0.000 description 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 2
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/52—Sulfur atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/48—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups having nitrogen atoms of sulfonamide groups further bound to another hetero atom
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/42—Singly bound oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/36—Nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- Veterinary Medicine (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| EP08161765 | 2008-08-04 | ||
| US16162709P | 2009-03-19 | 2009-03-19 | |
| PCT/EP2009/060061 WO2010015613A1 (en) | 2008-08-04 | 2009-08-03 | Organic compounds |
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| IL210836A0 IL210836A0 (en) | 2011-04-28 |
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| UA103198C2 (en) | 2008-08-04 | 2013-09-25 | Новартис Аг | Squaramide derivatives as cxcr2 antagonists |
| US8648118B2 (en) | 2010-12-17 | 2014-02-11 | Boehringer Ingelheim International Gmbh | Bicyclic ring system substituted amide functionalised phenols as medicaments |
| US8648070B2 (en) * | 2010-12-17 | 2014-02-11 | Boehringer Ingelheim International Gmbh | Bicyclic ring system substituted sulfonamide functionalised phenols as medicaments |
| AU2016201916A1 (en) * | 2011-09-02 | 2016-04-21 | Novartis Ag | Choline salt of an anti-inflammatory substituted cyclobutenedione compound |
| ES2655942T3 (es) * | 2011-09-02 | 2018-02-22 | Novartis Ag | Sal de colina de un compuesto anti-inflamatorio de ciclobutenodiona sustituida |
| FR2981935B1 (fr) * | 2011-10-28 | 2015-08-07 | Galderma Res & Dev | Nouveaux composes di-substitues de la diamino-3,4-cyclobutene-3-dione-1,2 utiles dans le traitement de pathologies mediees par des chimiokines. |
| FR2981934B1 (fr) * | 2011-10-28 | 2013-12-20 | Galderma Res & Dev | Nouveaux composes di-substitues de la diamino-3,4-cyclobutene-3-dione-1,2 utiles dans le traitement de pathologies mediees par des chimiokines. |
| EP2764866A1 (en) | 2013-02-07 | 2014-08-13 | IP Gesellschaft für Management mbH | Inhibitors of nedd8-activating enzyme |
| WO2014205127A2 (en) | 2013-06-18 | 2014-12-24 | New York University | Cellular factors involved in the cytotoxicity of staphylococcus aureus leukocidins: novel therapeutic targets |
| FR3030515B1 (fr) | 2014-12-23 | 2017-01-20 | Galderma Res & Dev | Nouveaux composes antagonistes des recepteurs cxcr1 et cxcr2 aux chimiokines, et leur utilisation dans le traitement de pathologies mediees par des chimiokines |
| TWI724056B (zh) | 2015-11-19 | 2021-04-11 | 美商卡默森屈有限公司 | Cxcr2抑制劑 |
| TWI734715B (zh) | 2015-11-19 | 2021-08-01 | 美商卡默森屈有限公司 | 趨化因子受體調節劑 |
| US10660909B2 (en) | 2016-11-17 | 2020-05-26 | Syntrix Biosystems Inc. | Method for treating cancer using chemokine antagonists |
| BR112020003245A2 (pt) * | 2017-08-14 | 2020-08-18 | Allergan, Inc. | 3-ciclobuteno-1,2-dionas 3,4-dissubstituído e uso do mesmo |
| BR112020008888A2 (pt) | 2017-11-16 | 2020-10-20 | Novartis Ag | terapias de combinação |
| AU2019205786B2 (en) | 2018-01-08 | 2023-12-14 | Chemocentryx, Inc. | Methods of treating generalized pustular psoriasis with an antagonist of CCR6 or CXCR2 |
| WO2019165315A1 (en) | 2018-02-23 | 2019-08-29 | Syntrix Biosystems Inc. | Method for treating cancer using chemokine antagonists alone or in combination |
| AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
| MY209296A (en) | 2018-09-21 | 2025-07-01 | Pfizer | N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamides useful as ccr6 inhibitors |
| AU2019402189B2 (en) | 2018-12-20 | 2023-04-13 | Novartis Ag | Dosing regimen and pharmaceutical combination comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives |
| BR112021015672A2 (pt) | 2019-02-15 | 2021-10-05 | Novartis Ag | Derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona substituída e usos dos mesmos |
| US20220144807A1 (en) | 2019-02-15 | 2022-05-12 | Novartis Ag | 3-(1-oxo-5-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
| CN112759549B (zh) * | 2019-11-05 | 2023-07-28 | 中国医学科学院药物研究所 | 3-取代氨基-4-((取代吡啶基)氨基)环丁-3-烯-1,2-二酮类化合物 |
| CN112851635B (zh) * | 2019-11-28 | 2022-09-16 | 中国医学科学院药物研究所 | 环状砜类化合物及其制备方法、用途和药物组合物 |
| EP4076660A1 (en) | 2019-12-20 | 2022-10-26 | Novartis AG | Uses of anti-tgf-beta antibodies and checkpoint inhibitors for the treatment of proliferative diseases |
| JP2023531676A (ja) | 2020-06-23 | 2023-07-25 | ノバルティス アーゲー | 3-(1-オキソイソインドリン-2-イル)ピぺリジン-2,6-ジオン誘導体を含む投与レジメン |
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| US20240115527A1 (en) * | 2020-11-05 | 2024-04-11 | Icahn School Of Medicine At Mount Sinai | Cxcr1/cxcr2 inhibitors for use in treating myelofibrosis |
| TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗TGFβ抗體及其他治療劑用於治療增殖性疾病之用途 |
| CN117355302A (zh) | 2021-04-30 | 2024-01-05 | 思维医学股份有限公司 | Lsd盐晶体形式 |
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| CZ20032639A3 (cs) | 2001-03-30 | 2004-04-14 | Smithkline Beecham Corporation | Způsoby přípravy sloučenin obsahujících fenol |
| US7132445B2 (en) * | 2001-04-16 | 2006-11-07 | Schering Corporation | 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands |
| MXPA03009441A (es) | 2001-04-16 | 2004-02-12 | Schering Corp | Ciclobuteno-1,2-dionas 3,4-disustituidas como ligandos del receptor de quimocina cxc. |
| US20040106794A1 (en) * | 2001-04-16 | 2004-06-03 | Schering Corporation | 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands |
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